skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


Title: The Art and Science of Building a Computational Model to Understand Hemostasis
Abstract Computational models of various facets of hemostasis and thrombosis have increased substantially in the last decade. These models have the potential to make predictions that can uncover new mechanisms within the complex dynamics of thrombus formation. However, these predictions are only as good as the data and assumptions they are built upon, and therefore model building requires intimate coupling with experiments. The objective of this article is to guide the reader through how a computational model is built and how it can inform and be refined by experiments. This is accomplished by answering six questions facing the model builder: (1) Why make a model? (2) What kind of model should be built? (3) How is the model built? (4) Is the model a “good” model? (5) Do we believe the model? (6) Is the model useful? These questions are answered in the context of a model of thrombus formation that has been successfully applied to understanding the interplay between blood flow, platelet deposition, and coagulation and in identifying potential modifiers of thrombin generation in hemophilia A.  more » « less
Award ID(s):
1848221
PAR ID:
10251741
Author(s) / Creator(s):
; ; ; ;
Date Published:
Journal Name:
Seminars in Thrombosis and Hemostasis
Volume:
47
Issue:
02
ISSN:
0094-6176
Page Range / eLocation ID:
129 to 138
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Miniature Magnetic Rotating Swimmers (MMRSs) are untethered machines containing magnetic materials. An external rotating magnetic field produces a torque on the swimmers to make them rotate. MMRSs have propeller fins that convert the rotating motion into forward propulsion. This type of robot has been shown to have potential applications in the medical realm. This paper presents new MMRS designs with (1) an increased permanent magnet volume to increase the available torque and prevent the MMRS from becoming stuck inside a thrombus; (2) new helix designs that produce an increased force to compensate for the weight added by the larger permanent magnet volume; (3) different head drill shape designs that have different interactions with thrombi. The two best MMRS designs were tested experimentally by removing a partially dried 1-hour-old thrombus with flow in a bifurcating artery model. The first MMRS disrupted a large portion of the thrombus. The second MMRS retrieved a small remaining piece of the thrombus. In addition, a tool for inserting, retrieving, and switching MMRSs during an experiment is presented and demonstrated. Finally, this paper shows that the two selected MMRS designs can perform accurate 3D path-following. 
    more » « less
  2. Metallic glasses have the potential to become transformative materials, but this is hindered by the lack of ability to accurately predict which metallic alloys will form good glasses. Current approaches are limited to empirical rules that often rely on parameters that are unknown until the glasses are made, rendering them not predictive. In this Perspective, properties of metallic liquids at elevated temperatures and how these might lead to better predictions for glass formation are explored. A central topic is liquid fragility, which characterizes the different dynamics of the liquids. What fragility is and how it might be connected to the liquid structure is discussed. Since glass formation is ultimately limited by crystallization during cooling, recent advances in crystal growth and nucleation are also reviewed. Finally, some approaches for improving glass stability and glass rejuvenation for improved plasticity are discussed. Building on a summary of results, some key questions are raised and a prospective for future studies is offered. 
    more » « less
  3. Abstract Achieving sustainable development requires understanding how human behavior and the environment interact across spatial scales. In particular, knowing how to manage tradeoffs between the environment and the economy, or between one spatial scale and another, necessitates a modeling approach that allows these different components to interact. Existing integrated local and global analyses provide key insights, but often fail to capture ‘meso-scale’ phenomena that operate at scales between the local and the global, leading to erroneous predictions and a constrained scope of analysis. Meso-scale phenomena are difficult to model because of their complexity and computational challenges, where adding additional scales can increase model run-time exponentially. These additions, however, are necessary to make models that include sufficient detail for policy-makers to assess tradeoffs. Here, we synthesize research that explicitly includes meso-scale phenomena and assess where further efforts might be fruitful in improving our predictions and expanding the scope of questions that sustainability science can answer. We emphasize five categories of models relevant to sustainability science, including biophysical models, integrated assessment models, land-use change models, earth-economy models and spatial downscaling models. We outline the technical and methodological challenges present in these areas of research and discuss seven directions for future research that will improve coverage of meso-scale effects. Additionally, we provide a specific worked example that shows the challenges present, and possible solutions, for modeling meso-scale phenomena in integrated earth-economy models. 
    more » « less
  4. Abstract Plant–animal mutualistic networks sustain terrestrial biodiversity and human food security. Global environmental changes threaten these networks, underscoring the urgency for developing a predictive theory on how networks respond to perturbations. Here, I synthesise theoretical advances towards predicting network structure, dynamics, interaction strengths and responses to perturbations. I find that mathematical models incorporating biological mechanisms of mutualistic interactions provide better predictions of network dynamics. Those mechanisms include trait matching, adaptive foraging, and the dynamic consumption and production of both resources and services provided by mutualisms. Models incorporating species traits better predict the potential structure of networks (fundamental niche), while theory based on the dynamics of species abundances, rewards, foraging preferences and reproductive services can predict the extremely dynamic realised structures of networks, and may successfully predict network responses to perturbations. From a theoretician's standpoint, model development must more realistically represent empirical data on interaction strengths, population dynamics and how these vary with perturbations from global change. From an empiricist's standpoint, theory needs to make specific predictions that can be tested by observation or experiments. Developing models using short‐term empirical data allows models to make longer term predictions of community dynamics. As more longer term data become available, rigorous tests of model predictions will improve. 
    more » « less
  5. Growth and yield models are essential tools in modern forestry, especially for intensively managed loblolly pine plantations in the southeastern United States. While model developers often have a good idea of where these models should be used with respect to geographic location, determining geographic bounds for model usage can be daunting. Such bounds provide suitable areas where model predictions are likely to behave as expected or identify areas where models may do a poor job of characterizing the growth of a resource. In this research, we adapted a niche model methodology, commonly used to identify suitable spots for species occurrence (maximum entropy), to identify areas for using growth and yield models built from plots established in the Lower Coastal Plain and Piedmont/Upper Coastal Plain in the southeastern United States. The results from this analysis identify areas with similar climatic envelopes and soil properties to the areas where data was collected to fit these growth and yield models. These areas show notable overlap with the areas prescribed for use by the evaluated growth and yield models and support practitioners use of these models throughout these regions. Furthermore, this methodology can be applied to different forest models built using large regional extents as long as climatic and soil values are available for each site. 
    more » « less